In a paper published online in advance in Nature this week, investigators at the Centre for Lymphoid Cancers and the Centre for Translational and Applied Genomics in Vancouver report their use of RNA-seq to show that a gene fusion involving the major histocompatibility complex class II transactivator CIITA occurs frequently in lymphoid cancers. The team found that "CIITA breaks are highly recurrent in primary mediastinal B-cell lymphoma and classical Hodgkin lymphoma," and that alterations of this gene "impact survival in primary mediastinal B-cell lymphoma."
In another Nature advance online publication, researchers in Sweden and Japan show that "chromosome length influences replication-induced topological stress" in S. cerevisiae. In its experimental manipulations, the team found that cells expressing mutated versions of the cohesion- and condensin-related Smc5/6 complex show "late replication delay of longer, but not shorter, chromosomes." As a result of its analysis, the team suggests that the "Smc5/6 complex facilitates fork rotation by sequestering nascent chromatid intertwinings that form behind the replication machinery."
An international research team led by investigators at Thomas Jefferson University in Philadelphia shows that FADD and RIP1 engage in a cell-type specific interplay that is "critical for the regulation of apoptosis and necrosis during embryogenesis and lymphocyte function." In Fadd knockout mice, the team found that "RIP1 deficiency allowed normal embryogenesis." However, the team found that "the developmental defect of Rip1−/− lymphocytes was partially corrected by FADD deletion." And in Fadd−/−Rip1−/− double-knockout mouse models, the team shows that "T cells are resistant to death induced by Fas or TNF-α and show reduced NF-κB activity."
In a trio of papers appearing online in advance in Nature Genetics this week, two international teams report on mutations in five pre-replication complex genes — ORC1, ORC4, ORC6, CDT1 and CDC6 — that cause Meier-Gorlin syndrome and show that "mutations in ORC1, encoding the largest subunit of the origin recognition complex, cause microcephalic primordial dwarfism resembling Meier-Gorlin syndrome." A third team reports its use of "marker-assisted mapping in multiple families from a founder population and traditional coding exon sequencing of positional candidate genes" to identify ORC4 missense mutations in affected individuals.